This study was designed to clarify results from an earlier pilot study that reported significant increases in three measures of chromosomal damage in lymphocytes of 12 children (ages 6-12) diagnosed with Attention DeficitHyperactivity Disorder (ADHD), following 3 months of treatment with methylphenidate-based medications (El-Zein et al., 2005). Significant protocol deficiencies in this study raised concerns about the conclusions (Preston et al., 2005) and prompted the design of this repeat study that employs a more extensive protocol and carefully monitored data collection. Recruitment and enrollment of study subjects is occurring through the Duke University Medical Center ADHD Program. In this study, we are investigating the same 3 measures of cytogenetic damage (micronuclei, sister chromatid exchanges, chromosomal aberrations) that were analyzed in the earlier pilot study. Universally established protocols for analysis of these three endpoints in lymphocytes are followed, and all laboratory procedures are conducted under Good Laboratory Practice guidelines. We are using the same schedule of analysis: measurement of the 3 cytogenetic endpoints in lymphocyte samples obtained from each subject prior to the initiation of drug treatment, and then again after 3 months of pharmacotherapy. Because Adderall, a combination of amphetamine salts, is increasingly used in the treatment of ADHD in children and now constitutes approximately 50% of all new drug prescriptions for ADHD patients, an investigation of cytogenetic endpoints in lymphocytes of Adderall-treated children has been added to this protocol to provide comparative data to clinicians and to patients. There are currently no published cytogenetic data for Adderall in humans. Adderall and methylphenidate are considered equally effective and physician choice is the factor determining which is prescribed for any particular patient. 60 children, age 6-12 years inclusive, of either sex, and of any ethnicity and race, diagnosed by Duke ADHD staff with ADHD, any subtype, for whom pharmacological treatment with stimulants is indicated will be enrolled in this study. 30 children will begin treatment with methylphenidate-based therapy and 30 children will begin treatment with Adderall. Assignment to study group is random because the two drug therapies are considered to be interchangeable. Over-recruitment of approximately 20% will take place to account for attrition and ensure a minimum of 30 subjects per treatment arm. No exclusions by ADHD subtype are necessary because there is no correlation between treatment, dose, and ADHD subtype. This number of subjects (60) will give us sufficient power to detect treatment-related cytogenetic changes or support negative observations. Study subjects are eligible for enrollment if they have no co-morbid psychological conditions, have no physical conditions that contraindicate stimulant treatment, are ADHD-drug naove, and have not received diagnostic x-rays in the past 3 months. All study subjects or their legal guardians will provide informed written consent. As of August 16, 2007, recruitment to the study is complete and all pre-drug blood samples have been obtained and processed. Final blood samples remain to be collected for approximately 8 study subjects. Preliminary data analysis has begun.